Role of the pro-inflammatory cytokines TNF-α and IL-1β in HIV-associated dementia

Human immunodeficiency virus-1 (HIV-1)-infected and immune-activated macrophages and microglia secrete neurotoxins. Two of these neurotoxins are the pro-inflammatory cytokines tumour necrosis factor-alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta), which are thought to play a major role in inducing neuronal death. Both TNF-alpha and IL-1 beta increase the permeability of the blood-brain barrier, through which subsequently HIV-infected monocytes can enter the brain. They both induce over-stimulation of the NMDA-receptor via several pathways, resulting in a lethal neuronal increase in Ca2+ levels. Additionally, TNF-alpha co-operates with several other proinflammatory mediators to enhance their toxic effects. Although most research has focused on the neurotoxic effects of TNF-alpha and IL-1 beta in HAD, there is also evidence that these cytokines can be neuroprotective. In this paper the effect of TNF-alpha and IL-1 beta on neuronal life and death in HAD is discussed.